The present invention generally relates to the field of fluid sensors and methods, and more particularly to the field of fluid sensors and methods for sensing fluids in unit operations involving separation, especially unit operations involving distillation, evaporation, extraction, drying and/or chemical reaction. Such fluid sensors and methods are suitable for use in process monitoring and/or process control systems and/or operations, and may be especially suitable for example, in the application of Process Analytical Technologies. The present invention relates, in preferred embodiments, to fluid sensor devices and methods adapted for monitoring and/or controlling distillation operations in fluid process systems, such as batch distillation operations or continuous distillation operations. The present invention relates, in particularly preferred embodiments, to process monitoring and/or process control, including devices and methods, for unit operations involving endpoint determination of a distillation, for example, as applied to a liquid-component-switching operation (e.g., a solvent switching operation), a liquid-liquid separation operation, a solute concentration operation, a dispersed-phase concentration operation, etc.
The method also relates to the application of fluid sensor devices in the conduct of other unit operations, including, e.g., evaporation, liquid/liquid extraction, oil seed extraction, drying of solids and various chemical reactions. Commercial applications for such fluid sensors and methods include, for example, process monitoring and/or process control for pharmaceutical development and/or pharmaceutical manufacturing, petroleum refining and industrial chemical manufacturing. In some embodiments, preferred fluid sensors and methods include mechanical resonators, such as flexural resonators. In other embodiments, preferred fluid sensors and methods include other types of sensors, including optical sensors such as refractive index sensors.
Distillation operations are well known in the art. See, generally, for example, McCabe et al., Unit Operations of Chemical Engineering, 3rd Ed., McGraw Hill, Inc. (especially pp. 511-606 and 657-677) (1976). See also, Perry et al., Perry's Chemical Engineer's Handbook, 6th Ed., McGraw Hill, Inc. (especially pp. 13-1 through 13-97) (1984). Generally, a distillations are a common unit operation performed in the pharmaceutical and fine chemical industries, industrial chemical manufacturing and petroleum refining. They are well known in the pharmaceutical industries, for example, in connection with solvent switch operations, and in various industries for the separation of fluid components and the isolation and/or purification of desired products.
In a solvent switch operation, for example, the goal is to switch a substance of interest (such as an active pharmaceutical or an intermediate in the synthesis and/or manufacture thereof) that is dissolved in one or more solvents to another (less volatile) solvent for subsequent processing. This unit operation avoids having to separately workup the substance (e.g., crystallize, filter and dry), and recharge the substance into a new solvent. Typically, a specification is set to define the end point of the solvent switch. This end-point can be defined by the concentration of residual solvent in the residual liquid phase. This specification is typically based on the sensitivity of subsequent processing steps on the presence of the residual solvent. In traditional approaches, such distillation operations are monitored using process conditions such as temperature and/or pressure and/or flow, and end-points are typically determined or confirmed by manual sampling and analysis. For example, a sample would typically be manually obtained from the still or other process vessel. Manual sampling could require an operator, for example, to cool the fluid system to an appropriate temperature (for access and handling), and in some cases to donn appropriate safety clothing, access the fluid system (e.g., through a manway), manually withdraw a sample (e.g., using a dipstick) and transport the sample for off-line analysis (e.g., to an off-site analytical lab for analysis, such as gas chromatography). Significantly, for meaningful analysis, the batch must be held under stable conditions during sampling, transport and off-line measurement. In certain operations, such sampling steps can add potentially 2-3 hours or more onto the batch timecycle.
Hence, there is a need in the art to improve process monitoring and control of separation operations such as distillation operations.
Similar issues are encountered in monitoring and controlling various other fluid process operations, including liquid/liquid extraction, liquid/solid extraction, evaporation, drying and various chemical reactions. Control issues arise in the operation of both batch and continuous processes. In a liquid/liquid extraction process, for example, there is a need to control the operation so that the extract is sufficiently enriched in the solute to be extracted and residual solute content of the raffinate is reduced to a desired level. In evaporation processes, such as, for example, the concentration of caustic solutions emanating from chloralkali cells, there is a need to reach a desired level of concentration and to monitor entrainment of alkali hydroxide and/or alkali metal chlorides in the overhead vapor. In drying operations, there is a need to determine the residual moisture or other volatile content of the solids to be dried. In chemical reactions, there is a need to monitor conversion of reactants to products and in some instances to monitor the formation of by-products. Reaction control presents unique problems in the case of polymerization reactions. Other and somewhat differing issues are presented in the formation of lower molecular weight products, e.g., in chemical or pharmaceutical manufacturing operations.
Control problems are confronted in both batch and continuous processes. In batch processes, the control issue may devolve to identification of an end point of the operation, whether it be distillation, extraction, drying or chemical reaction. In a continuous process, control may typically require adjustment of flow rates, temperatures and pressures to maintain the composition of a product stream, recycle stream, or other process stream at a target value. In either case, there is a need to continually or periodically monitor the composition of a product or other process fraction and adjust process conditions, batch cycles, etc. to maintain a product within a target specification.
On-line measurement techniques are growing in popularity in the process industries where they are known, especially among fine chemical manufacturers, as “Process Analytical Technologies (PAT).” On-line compositional measurements enable the operator to determine the quality of a product batch, or of process material at a particulate point in the flow path of a continuous process without the waste of time and productivity that results from resort to off-line analyses. For various applications, including the monitoring of reactors and batch distillations, e.g., solvent switch distillation, the currently most robust on-line measurement techniques are Near Infrared (NIR) and Fourier Transform Infrared (FTIR). However, because these techniques require substantial capital investment, extensive calibration models, and relatively expensive maintenance, they are difficult to apply in relatively complex operations, especially where there are plural phases in a sample (e.g., in slurry processing where sample handling devices may become plugged with solids), and are difficult to justify in relatively simple operations such as solvent switch wherein at least rough approximations of distillation end points may be determined by monitoring head pressure, overhead vapor temperature and/or still pot temperature.
Effective approaches for measuring characteristics of fluids using mechanical resonators are disclosed in commonly-owned U.S. Pat. Nos. 6,401,519; 6,393,895; 6,336,353; 6,182,499; 6,494,079 and EP 0943091 B1, each of which are incorporated by reference herein for all purposes. See also, Matsiev, “Application of Flexural Mechanical Resonators to Simultaneous Measurements of Liquid Density and Viscosity,” IEEE International Ultrasonics Symposium, Oct. 17-20, 1999, Lake Tahoe, Nev., which is also incorporated by reference herein for all purposes. The use of a quartz oscillator in a sensor has been described as well in U.S. Pat. Nos. 6,223,589 and 5,741,961, and in Hammond, et al., “An Acoustic Automotive Engine Oil Quality Sensor”, Proceedings of the 1997 IEEE International Frequency Control Symposium, IEEE Catalog No. 97CH36016, pp. 72-80, May 28-30, 1997.
Sensors involving mechanical resonators are known in the art for use in several applications. For example, U.S. Pat. No. 6,182,499 to McFarland et al., discloses mechanical resonator sensors for evaluating fluid properties, especially of an array of fluids in parallel (i.e., simultaneously) and sequentially (e.g., by scanning). Also, PCT Application WO 2004/036207 discloses mechanical resonator sensors in connection with environmental control systems, such as refrigeration systems. PCT application WO 2004/036191 discloses mechanical resonator sensors in connection with machines, such as transportation vehicles.
The use of other types of sensors is also known in the art in connection with various applications. For example, the use of acoustic sensors has been addressed in applications such as viscosity measurement in J. W. Grate, et al, Anal. Chem. 65, 940A948A (1993)); “Viscosity and Density Sensing with Ultrasonic Plate Waves”, B. A. Martin, S. W. Wenzel, and R. M. White, Sensors and Actuators, A21-A23 (1990), 704708; “Preparation of chemically etched piezoelectric resonators for density meters and viscometers”, S. Trolier, Q. C. Xu, R. E. Newnham, Mat.Res. Bull. 22, 1267-74 (1987); “On-line Sensor for Density and Viscosity Measurement of a Liquid or Slurry for Process Control in the Food Industry”, Margaret S. Greenwood, Ph.D. James R. Skorpik, Judith Ann Bamberger, P.E. Sixth Conference on Food Engineering, 1999 AIChE Annual Meeting, Dallas, Tex.; U.S. Pat. Nos. 5,708,191; 5,886,250; 6,082,180; 6,082,181; and 6,311,549; and “Micromachined viscosity sensor for real-time polymerization monitoring”, O. Brand, J. M. English, S. A. Bidstrup, M. G. Allen, Transducers '97, 121-124 (1997). See also, U.S. Pat. No. 5,586,445 (“Low Refrigerant Charge Detection Using a Combined Pressure/Temperature Sensor”).
As noted above, there remains a need in the art for alternative or improved sensor devices and methods for efficiently sensing, monitoring or evaluating fluids in unit operations involving separations such as unit operations involving distillation, extraction, evaporation, drying and/or chemical reaction. Examples of commercial areas in which such a need exists include for example, such fluid process systems used in connection with the petroleum, chemical, and pharmaceutical industries. In particular, there remains a need in the art for effectively sensing one or more fluids in unit operations involving separations using relatively straightforward, cost-effective, scalable systems and methods, with requisite accuracy and precision.